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• W1966009005 abstract "ABSTRACT Tolvaptan is an orally effective nonpeptide arginine vasopressin (AVP) V 2 ‐receptor antagonist synthesized by Otsuka Pharmaceutical Co., Ltd. In in vitro receptor‐binding studies, tolvaptan blocked the binding of [ 3 H]AVP to human V 2 receptors with 29‐fold greater selectivity than that for V 1a receptors, and showed no inhibition of V 1b receptors. Tolvaptan inhibited not only the binding of [ 3 H]AVP but also the AVP‐induced production of cyclic AMP in human V 2 ‐receptor–expressing HeLa cells. In addition, tolvaptan has no intrinsic V 2 receptor agonistic effect. In in vivo studies, tolvaptan showed marked aquaresis in healthy and diseased animals. In rat models with acute and chronic hyponatremia, tolvaptan improved hyponatremia, resulting in the prevention of death, and improved organ water retention. Tolvaptan reduced cardiac preload without unfavorable effects on renal functions, systemic hemodynamics, or circulating neurohormones in dogs with heart failure (HF). Furthermore, in animal models of human polycystic kidney disease (PKD), tolvaptan showed a decrease in kidney weight as well as in cyst and fibrosis volume. In clinical trials including the “ACTIV in CHF” study, tolvaptan in addition to standard therapy increased fluid loss resulting in decreased body weight, and improved edema and serum sodium without affecting blood pressure, heart rate, or renal functions in patients with HF. In patients with hyponatremia, treatment with tolvaptan without fluid restriction appeared to be more effective than fluid restriction alone at correcting hyponatremia without an increase in adverse events. A phase III trial EVEREST is currently being conducted to evaluate the long‐term efficacy and safety of tolvaptan in hospitalized patients with severe HF. In conclusion, tolvaptan offers the possibility of a useful therapy in hyponatremia, congestive heart failure, and various other diseases that are associated with volume overload. Furthermore, tolvaptan is also expected to be effective in the treatment of PKD." @default.
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• W1966009005 date "2007-03-01" @default.
• W1966009005 modified "2023-10-18" @default.
• W1966009005 title "Tolvaptan, an Orally Active Vasopressin V2-Receptor Antagonist-Pharmacology and Clinical Trials" @default.
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• W1966009005 doi "https://doi.org/10.1111/j.1527-3466.2007.00001.x" @default.
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